Biomol Ther.  2015 Sep;23(5):449-457. 10.4062/biomolther.2015.034.

A Dunnione Compound MB12662 Improves Cisplatin-Induced Tissue Injury and Emesis

• Park D
• Jo IG
• Jang JY
• Kwak TH
• Yoo SK
• Jeon JH
• Choi EK
• Joo SS
• Kim O
• Kim YB

• KMID: 2380294
• DOI: http://doi.org/10.4062/biomolther.2015.034

Abstract

The present study was aimed to investigate the effects of MB12662, a synthetic dunnione compound, on cisplatin-induced vomiting reflexes and intestinal, renal, immune system, and hematopoietic toxicities in ferrets and mice, respectively. Male ICR mice were orally administered MB12662 (5, 10, 25 or 50 mg/kg) for 10 days, during which intraperitoneally challenged with cisplatin (3.5 mg/kg) from day 4 to 7, and sacrificed on day 10 for the pathological examination. Male ferrets were orally administered MB12662 (25, 50 or 100 mg/kg) for 7 days, subcutaneously challenged with cisplatin (5 mg/kg), and monitored for vomiting reflexes and survival of the animals. Four-day injection of cisplatin (3.5 mg/kg) to mice caused body weight loss and degeneration and atrophy of intestinal villi, reducing villi/crypt ratio to a half level of control animals. Cisplatin also induced renal and hepatic toxicities, and depletion of splenocytes and bone marrow progenitor cells. The systemic toxicities including decreased villi/crypt ratio, immune system atrophy, splenocyte depletion, and decreased cellularity in bone marrow were improved by MB12662. Cisplatin (5 mg/kg) induced retching and emetic responses of ferrets, which were remarkably attenuated by MB12662 in a dose-dependent manner. All the ferrets pretreated with MB12662 survived the challenge of cisplatin, in comparison with 40% mortality in vehicle-treated animals, and blood parameters of nephrotoxicity and hepatotoxicity were markedly recovered. It is expected that MB12662 could be a candidate for the body protection against burden, including emesis, of chemotherapeutic agents.

Keyword

Cisplatin; Emesis; Intestinal injury; Nephrotoxicity; Dunnione; MB12662

MeSH Terms

Animals
Atrophy
Body Weight
Bone Marrow
Cisplatin
Ferrets
Humans
Immune System
Male
Mice
Mice, Inbred ICR
Mortality
Reflex
Stem Cells
Vomiting*
Cisplatin